Conditions in the body need to be just right for optimal function. For example, temperature, blood sugar, and immune system activity must all be regulated for optimal function. Signaling systems made up of transmitters, receptors, and enzymes control these responses. The endocannabinoid system is involved in balancing brain cell firing (pictured above) and inflammation reactions.
molecules produced to transmit signals. They are produced in the cell and transported out to communicate with other cells by binding to receptors. To prevent a build-up of transmitter molecules, enzymes will degrade them over time.
produced by the body from the metabolism of omega-6 fatty acid. Binds to CB1 & CB2 receptors. Nicknamed the “bliss molecule”.
A cannabinoid produced by the body, occurs in higher concentrations in central nervous system. Binds CB1 & CB2 receptors.
proteins on the cell membrane that listen for signals. When a cannabinoid binds and activates the receptor, a cellular response will be initiated.
binding activity linked to mood, memory processing, pain sensation, and the familiar psychoactive effects of cannabis
binding activation linked to immune responses, cell proliferation, but is NOT linked to the high produced by cannabis.
Sites and functions of the endocannabinoid system
The endocannabinoid system has long been thought to function only within the nervous system. However, new research has shown that endocannabinoid signaling affects the activity of many organ systems.
In the nervous system, it regulates neuron firing. Binding of CB1 in the brain has been linked to euhporic states and altered cognitive processing. CB1 and CB2 activation in peripheral nerves affects pain signaling.
Across the body’s tissues, the endocannabinoid system controls inflammatory responses. When an infection is detected, immune cells become more active and gather at the site of infection. If overstimulated, this response may become too aggressive and cause damage to healthy cells. CB2 stimulation has been shown to control B-cell maturation and reduce pro-inflammatory signaling. Interestingly, the system responds to injury and inflammation by creating more receptors in affected tissues.
Other sites and functions associated with these receptors are shown below.
Cannabinoid receptor locations and activity:
Skeptics often wonder how cannabinoids can present such a diverse array of effects on different people. Research has uncovered a number of conditional interactions between CB1 and other receptors which may explain (and complicate) our understanding of the endocannabinoid system functions. These protens link with CB1 on the cell membrane, changing the behavior of each receptor.
- CB1 + μOR [opoid receptor] — When both activated has been shown to reduce pain blocking effects
- CB1 + δOR [opoid receptor] :: increased linkage during chronic pain, may improve mood
- CB1 + HT2A [serotonin receptor] :: CB1 activation may co-activate HT2A, may be cause of memory loss in cannabis users
- CB1+ D2 [dopamine receptor] :: both activated increases linkage frequency, effects unknown
- CB1 + A2A [adenosine receptor] :: caffeine receptor, co-activation reduces signaling, effects unknown
Implications & Opportunities for therapy
The effects of CB1 interacting with other signaling pathways are still being explored. It also supports how supplemental use of CB1 binding compounds (like THC) may be used an alternative route to address chronic pain.
As understanding of the endocannabinoid system increases, the potential of plant extracted cannabinoids is being realized. Research and clinical trials are catching up to anecdotal evidence supporitng the benefits of cannabis. However, other naturally occuring molecules can also help achieve internal balance.
Plants and their cannabinoids
- CANNABIS: THC, CBD, CBN, CBC, CBL, CBV, THCV, CBDV, CBCV, CBGV, CBGM, CBE, CBT. (Clinical trials ongoing relate to pain, MS, and epilepsy)
- ECHINACEA: alkylamides that interact with CB2 for immune support
- HELICHRYSUM: some strains contain compounds like CBG
- PEPPERCORNS: contains the terpene beta-caryophyllene which will selectively bind CB2